Norihiro Nakamura

Publications (2)22.98 Total impact

• Article: Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation.

  Lillian Cohn, Bithi Chatterjee, Filipp Esselborn, Anna Smed-Sörensen, Norihiro Nakamura, Cécile Chalouni, Byoung-Chul Lee, Richard Vandlen, Tibor Keler, Peter Lauer, Dirk Brockstedt, Ira Mellman, Lélia Delamarre
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  ABSTRACT: Human BDCA3(+) dendritic cells (DCs), the proposed equivalent to mouse CD8α(+) DCs, are widely thought to cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for cross presentation or a generally enhanced ability to present antigens on MHCI. We compared presentation by BDCA3(+) DCs with BDCA1(+) DCs using a quantitative approach whereby antigens were targeted to distinct intracellular compartments by receptor-mediated internalization. As expected, BDCA3(+) DCs were superior at cross presentation of antigens delivered to late endosomes and lysosomes by uptake of anti-DEC205 antibody conjugated to antigen. This difference may reflect a greater efficiency of antigen escape from BDCA3(+) DC lysosomes. In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1(+) DCs were as efficient at cross presentation as BDCA3(+) DCs. Because BDCA3(+) DCs and BDCA1(+) DCs were also equivalent at presenting peptides and endogenously synthesized antigens, BDCA3(+) DCs are not likely to possess mechanisms for cross presentation that are specific to this subset. Thus, multiple DC populations may be comparably effective at presenting exogenous antigens to CD8(+) T cells as long as the antigen is delivered to early endocytic compartments.
  Journal of Experimental Medicine 04/2013; · 13.85 Impact Factor
• Source

  Available from: PubMed Central

  Article: Influenza A virus infection of human primary dendritic cells impairs their ability to cross-present antigen to CD8 T cells.

  Anna Smed-Sörensen, Cécile Chalouni, Bithi Chatterjee, Lillian Cohn, Peter Blattmann, Norihiro Nakamura, Lélia Delamarre, Ira Mellman
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  ABSTRACT: Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was -300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection.
  PLoS Pathogens 03/2012; 8(3):e1002572. · 9.13 Impact Factor